EP2250149B1

EP2250149B1 - Method for the production of arginine bicarbonate

Info

Publication number: EP2250149B1
Application number: EP09708628.4A
Authority: EP
Inventors: Rajnish Kohli; Richard Robinson; Donghui Wu; Wilbens Josias
Original assignee: Colgate Palmolive Co
Current assignee: Colgate Palmolive Co
Priority date: 2008-02-08
Filing date: 2009-02-06
Publication date: 2019-09-18
Anticipated expiration: 2029-02-06
Also published as: AR072341A1; JP2011511794A; CA2706353C; RU2010137275A; CO6290754A2; EP2250149A1; MX2010004570A; RU2468003C2; BRPI0906451A2; TWI389876B; ZA201003678B; MY155330A; CA2706353A1; US20120088930A1; CN101939292A; JP5520235B2; US8399704B2; EP2250149A4; AU2009212323B2; TW200948761A

Description

FIELD OF THE INVENTION

The invention relates to novel methods for production of arginine bicarbonate.

BACKGROUND

Arginine bicarbonate has use in various industrial applications, including use in personal care compositions, e.g., oral care compositions. See e.g., US patent 6,524,558 . As the industrial requirements for arginine bicarbonate increases, so will the need for improved processes and methods to manufacture the same.
Arginine bicarbonate may be produced by bubbling carbon dioxide gas through a saturated arginine aqueous solution. However, the efficiency of the existing process needs to be improved. The existing process is slow, requiring 24 to 48 hours to complete the reaction. Carbon dioxide has very limited solubility in water, and releasing the gas into the solution produces a maximum concentration of about 1.2x10^-5 M at room temperature and its natural partial pressure (3.5x10^-4 atmosphere). The solubility of arginine in water is only about 15% weight/weight at room temperature. Producing a concentrated arginine bicarbonate solution (e.g., about 40%) requires the continual addition of arginine to the solution, thereby increasing production time and requires constant monitoring of the reaction. Thus there is a need to improve methods to manufacture arginine bicarbonate.

SUMMARY OF THE INVENTION

The present invention is directed to an improved method for manufacturing arginine bicarbonate. The method represents a significant improvement over existing techniques, as a concentrated solution of arginine and bicarbonate anions may be produced in as little as about 10 minutes (vs. about 24 - 48 hours using the prior art methods), followed by faster and easier recovery processes of arginine bicarbonate salt from the solution since arginine bicarbonate solution at significantly higher concentration, e.g., 60% w/w, can be produced.
The present invention refers to a method to produce arginine bicarbonate comprising: reacting an arginine slurry having 30% to 70% by weight of arginine in water with carbon dioxide under controlled temperature of greater than 50°C and pressure, wherein the carbon dioxide is added to the arginine in water in a sealed reaction vessel to form a solution comprising arginine and bicarbonate anion, wherein the partial pressure of carbon dioxide is 34 kPa to 1034 kPa (5 psi to 150 psi); permitting the reactor contents to cool to 0-40°C, and recovering arginine bicarbonate from the solution (referred to as "method 1.0" in the following).
Embodiments of the present invention include Methods:

1.4 Of method 1.0 wherein the arginine of step (i) comprises arginine free base;
1.5 Of method 1.0 wherein the arginine is L-arginine;
1.6 Of method 1.0 wherein the arginine of step (i) comprises a salt;
1.7 Of any of the foregoing methods wherein the arginine of step (i) comprises arginine hydroxide;
1.8 Of any of the foregoing methods wherein the arginine of step (i) is comprises arginine hydrochloride;
1.9 Of any of the foregoing methods wherein the arginine of step (i) is a mixture comprising arginine in free base form and an arginine salt;
1.10 Of any of the preceding methods wherein the carbon dioxide is added to the slurry as a solid, e.g., dry ice;
1.11 Of method 1.0 wherein the carbon dioxide is added to the slurry as a gas;
1.15 According to the invention the carbon dioxide partial pressure is 34 kPa to 1724 kPa (5 psi to 250 psi), e.g., 345 kPa to 1034 kPa (50 to 150 psi), e.g., 414 kPa to 689 kPa (60 to 100 psi);
1.16 Of any of the preceding methods wherein the arginine slurry and carbon dioxide are maintained under pressure for a period greater than about 1 minute, e.g., 1 minute to 120 minutes, e.g., from 1 minute to 30 minutes;
1.19 Of any of the preceding methods wherein the arginine slurry is cooled to 0°C to 40°C, e.g., 0°C to 20°C;
1.20 Of any of the preceding methods wherein the arginine slurry and carbon dioxide is agitated;
1.21 Of any of the preceding methods wherein the carbon dioxide forms carbonic acid when dissolved in the arginine slurry;
1.22 Of method 1.20 wherein the carbonic acid forms bicarbonate anion in solution;
1.23 Of any of the preceding methods wherein the initial arginine slurry has a pH of 10 to 14;
1.24 Of any of the preceding methods wherein the finished arginine bicarbonate solution has a pH of 7 to 10;
1.25 Of any of the preceding methods wherein the arginine bicarbonate is recovered from the solution by evaporation;
1.30 Of any of the preceding methods further comprising adding a bicarbonate salt, e.g., sodium bicarbonate, to the slurry or solution;
1.31 Of any of the preceding methods wherein calcium carbonate is added to the slurry or solution;
1.32 Of method 1.27 wherein the arginine bicarbonate is co-precipitated with the calcium carbonate.
1.33 Any of the foregoing methods wherein the arginine bicarbonate solution is used in formulation of a product, without fully recovering and purifying the arginine bicarbonate;
1.34 Any of the foregoing reactions wherein the pH of the solution is adjusted to pH 8 to 9;
1.35 Any of the foregoing methods wherein the temperature is initially raised to greater than 50°C, e.g., to 50 to 70°C, e.g., 55°C (e.g., to enhance the solubility of the arginine), e.g., for 5 to 60 minutes, then lowered to from 0°C to 40°C, e.g., 0°C to
20°C (e.g., to enhance the solubility of the carbon dioxide, drive the reaction to completion, and permit the reaction vessel to be opened without excessive release of carbon dioxide from the solution.).
1.36 Any of the foregoing methods wherein the initial pH of the solution is about 12.
1.37 Any of the foregoing methods wherein the final pH of the solution is 8 to 9.0.

DETAILED DESCRIPTION OF THE INVENTION

The present invention involves a surprisingly simple reaction to produce arginine bicarbonate salt by reacting carbon dioxide and an arginine slurry under controlled temperature and pressure to form an arginine and bicarbonate anion solution, wherein the salt is then recovered from solution. The initial reaction is faster than existing methods, about 10 minutes vs. over 24 hours, and yields a more concentrated solution of arginine and bicarbonate anion (ca. 60% vs. ca. 40%).
The present method begins with the formation of an arginine slurry comprising arginine and a solvent, preferably water. As arginine free base is only slightly soluble at water at room temperature, the addition of arginine to water forms a slurry, wherein a majority of the arginine is insoluble. Any form of arginine may be utilized to form the slurry, e.g., arginine free base (in D or L form, usually L-form), or an arginine salt. It is understood that various arginine salts, e.g., hydrochloride, and pharmaceutically acceptable salts, may be substantially more soluble in water than arginine free base, and this may allow for the production of more concentrated arginine and bicarbonate anion solution. Thus, salts may be used or mixtures of free base and salts may be used in combination to form the slurry.
The slurry is produced by the addition of 30% to 70% weight of arginine to water the solvent, e.g., 40 % to 60%. The slurry may then be agitated to create a homogenous mixture. The initial pH of the slurry is generally about 12 for arginine free base, e.g., 10 to 13.
In one embodiment, the slurry may be heated to to 55°C to 60°C, to 65°C, or to 70°C to increase the solubility of the arginine.
The reaction between carbon dioxide and water is well known in the art, wherein carbonic acid is initially formed, and disassociates into bicarbonate and hydrogen ions. The bicarbonate then further disassociates into carbonate and an additional hydrogen ion. In the present invention, carbon dioxide is added to the arginine slurry in a pressurized vessel to form bicarbonate anions, resulting in a protonated arginine (cation) and bicarbonate anion solution.
The solubility of carbon dioxide into the slurry may be increased by decreasing the temperature of the solution; however, this decreases the solubility of the arginine. Thus, a careful balance must be maintained between solubility of both components. Thus, in one embodiment, the pressurized vessel may be temperature controlled. The arginine slurry is preferably at a relatively high temperature, when the carbon dioxide is added to the arginine slurry, and thereafter the arginine slurry is permitted to cool to a relatively low temperature, e.g. from 0°C to 40°C.
One method of decreasing the temperature of the arginine slurry so as to increase the solubility of carbon dioxide into the slurry is to provide the carbon dioxide at a lower temperature than that of the slurry, for example by introducing carbon dioxide as dry ice, or a cooled gas. Preferably, carbon dioxide gas is used in the present reaction. Additionally, direct cooling of the slurry may be carried out.
The solubility of carbon dioxide into the slurry may be increased by increasing the partial pressure of the carbon dioxide in the reaction vessel. Thus, the reaction between the carbon dioxide and the arginine slurry may occur at 34 kPa to 1034 kPa (
5 psi to 150 psi), e.g., 345 kPa (50 psi), to 414 kPa (60 psi), to 483 kPa (70 psi), to 552 kPa (80 psi), to 620 kPa (90 psi), to 689kPa (100 psi), to 758 kPa (110 psi), to 827 kPa (120 psi), or to 965 kPa (140 psi).
The reaction between the arginine slurry and carbon dioxide is then allowed to proceed for 1 to 120 minutes. The completion of the reaction may be gauged by monitoring the presence of undissolved arginine in the slurry, as arginine in the presence of bicarbonate anions are highly soluble compared to the arginine slurry. Another method to monitor the reaction is to measure its solution's pH in the reaction vessel directly, or sample the solution and measure its pH in an open container at room temperature.
Depending on the completion of the reaction, preferably, no solid arginine remains, and the arginine and bicarbonate anion solution is clear and colorless, additional carbon dioxide may be added to the reaction vessel.
Following the production of the arginine bicarbonate solution, the arginine bicarbonate salt may be recovered by any means known by those of skill in the art. In one embodiment, the solvent is evaporated, e.g., by heating, spray drying, or freeze drying. In another embodiment, the salt is precipitated from solution by the addition of alcohol.
The present methods may be utilized to produce arginine bicarbonate in single batches, or may be used in a continuous process, such as in continuous stirred tank reactors, fluidized bed reactors, and plug flow reactors.

EXAMPLE 1 - preparation of arginine slurry

A slurry of pH 12 containing 50% L-arginine by weight and 50% water by weight is prepared by mixing 85 g of L-arginine with 85 g of water at room temperature. The slurry is heated to 55° C under gentle agitation. Approximately 50% of the L-arginine is determined to be dissolved by visual observation.

EXAMPLE 2

25 grams of dry ice particles are added to the slurry produced in EXAMPLE 1, and the mixture is transferred to a pressurized vessel. The dry ice is allowed to sublime in order to purge atmospheric air from the vessel, and then the vessel is sealed. Pressure in the vessel is allowed to increase to 552 kPa (80 psi), and the solution is maintained under pressure for 3 minutes. The vessel is opened, a small amount of unreacted arginine is observed at the bottom of the vessel.

EXAMPLE 3

The solution of EXAMPLE 2 is stirred with a spatula to make a suspension. 10 grams of dry ice is added to the vessel, and the vessel is sealed. The pressure is allowed to increase to, and maintained at 621 kPa (90 psi). The vessel is opened after 3 minutes, and a thick clear colorless solution is observed without precipitation. The solution has dropped to 12°C.producing an arginine bicarbonate solution of about 60% concentration, and a final pH of 8.79. Arginine bicarbonate salt is recovered by freeze drying.

EXAMPLE 4

The slurry produced in EXAMPLE 1 is transferred to a pressurized vessel, and aerated with carbon dioxide gas to obtain a carbon dioxide partial pressure of 103 kPa (15 psi) for 5 minutes. The temperature of the reactants is lowered to 10°C. An arginine bicarbonate anion solution is formed, and arginine bicarbonate salt is recovered by spray drying.

Claims

A method to produce arginine bicarbonate comprising: reacting an arginine slurry having 30% to 70% by weight of arginine in water with carbon dioxide under controlled temperature of greater than 50°C and pressure, wherein the carbon dioxide is added to the arginine in water in a sealed reaction vessel to form a solution comprising arginine and bicarbonate anion, wherein the partial pressure of carbon dioxide is 34 kPa to 1034 kPa (5 psi to 150 psi); permitting the reactor contents to cool to 0-40°C, and recovering arginine bicarbonate from the solution.
The method of claim 1, wherein the arginine comprises a free base.
The method of any of the preceding claims, wherein the arginine is selected from L-arginine, D-arginine, or a mixture thereof.
The method of any of the preceding claims, wherein the arginine comprises an arginine salt, optionally wherein the arginine is selected from arginine hydroxide, arginine hydrochloride, or a mixture thereof.
The method of any of the preceding claims, wherein the carbon dioxide is provided to the reaction as a solid.
The method of any of the claims 1 to 5, wherein the carbon dioxide is provided to the reaction as a gas under pressure.
The method of any of the preceding claims, wherein the arginine slurry and carbon dioxide are maintained under pressure for a period of 1 minute to 120 minutes.
The method any of the preceding claims, wherein the arginine slurry has a pH of 10 to 14 or wherein the arginine bicarbonate solution has a pH of 7 to 10.
The method of any of the preceding claims, wherein the arginine bicarbonate is recovered from the solution by evaporation.